Olaparib Improves PFS as Frontline Maintenance in Ovarian Cancer

Olaparib (Lynparza) tablets reduced the risk of disease progression or death compared with placebo as frontline maintenance therapy for women with BRCA-positive advanced ovarian cancer, according to findings from the randomized phase III SOLO-1 trial.

The median PFS for patients taking maintenance olaparib was 8.4 months, compared to 4.8 months for the control group (HR, 0.35; P <.0001). For those with BRCA mutations, the median PFS was 11.2 versus 4.3 months for placebo, representing an 82% reduction in the risk of progression or death (HR, 0.18; P<.0001).

In the third interim analysis of Study 19, across the full study the median OS was 29.8 months in the olaparib group and 27.8 months in the placebo group (HR, 0.73; 95% CI, 0.55-0.96; nominal P = .02483). In the BRCA mutation group (n = 136), median OS was 34.9 months for the olaparib group and 30.2 months for placebo (HR, 0.62; 95% CI, 0.41-0.94; nominal P = .02480). However, these were not considered to be statistically significant.

According to the FDA, the most commonly observed adverse events (AEs) for olaparib were anemia, nausea, fatigue (including asthenia), vomiting, nasopharyngitis, diarrhea, arthralgia/myalgia, dysgeusia, headache, dyspepsia, decreased appetite, constipation, and stomatitis. The most common laboratory abnormalities were decrease in hemoglobin, increase in mean corpuscular volume, decrease in lymphocytes, decrease in leukocytes, decrease in absolute neutrophil count, increase in serum creatinine, and decrease in platelets.

In the SOLO2 trial, which assessed the tablets specifically, grade ≥3 AEs were reported for 36.9% of patients treated with olaparib versus 18.2% with placebo. The most common non-hematologic AEs for olaparib were nausea (75.9%), fatigue/asthenia (65.6%), vomiting (37.4%), diarrhea (32.8%), and abdominal pain (24.1%). The incidence of serious hematologic AEs included anemia (19.5%), neutropenia (5.1%), and thrombocytopenia (1.0%).

The median duration of treatment was 19.4 months for olaparib versus 5.6 months with placebo. Forty-five percent of patients required a dose interruption in the olaparib group versus 18% in the placebo arm and dose reductions were required for 27% and 3% of patients, respectively. The most frequent AEs leading to dose interruption or reduction were anemia (22%), neutropenia (9%), and fatigue/asthenia (8%).
Olaparib is also approved by the FDA for the treatment of women with germline BRCA-positive advanced ovarian cancer following at least 3 lines of chemotherapy.